Glia are the main source of lactate utilized by neurons for recovery of function posthypoxia.
Experiments are described in which a rat hippocampal slice preparation was used along with the metabolic glial inhibitor, fluorocitrate (FC), to investigate the role of glial-made lactate and its shuttling to neurons in posthypoxia recovery of synaptic function. After testing two less effective concentrations of FC, only 10.1 +/- 6.5% of slices treated with 100 microM of the metabolic toxin recovered synaptic function at the end of 10-min hypoxia and 30-min reoxygenation. In contrast, 79.6 +/- 7.4% of control, untreated slices recovered synaptic function after 10-min hypoxia and 30-min reoxygenation. The low rate of recovery of synaptic function posthypoxia in FC-treated slices occurred despite the abundance of glucose present in the medium before, during, and after hypoxia. The amount of lactate produced by FC-treated slices during the hypoxic period was only 62% of that produced by control, untreated slices. Supplementing FC-treated slices with exogenous lactate significantly increased the posthypoxia recovery rate of synaptic function. These results strongly support our previous findings concerning the mandatory role of lactate as an aerobic energy substrate for the recovery of synaptic function posthypoxia and clearly show that the bulk of the lactate needed for this recovery originates in glial cells.
Schurr
A
A
Department of Anesthesiology, University of Louisville School of Medicine, KY 40292, USA. a0schu01@ulkyvm.louisville.edu
Payne
R S
RS
Miller
J J
JJ
Rigor
B M
BM
D000818:Animals; D002951:Citrates / Q000494:pharmacology; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology
D002951:Citrates; D019344:Lactic Acid; C007744:fluorocitrate